Project 2: Mechanisms of Shock Wave Action for Improved SWL The goal of Project 2 is to find ways to improve lithotripsy. To reach this goal we have identified three main objectives. We will: 1) provide an objective basis for the choice of lithotripter settings for SW-rate and power used in treating kidney stones (Aims 1 and 2), 2) determine the role of cavitation bubble cluster dynamics in stone fragmentation and find ways for the urologist to enhance the positive action of cavitation in stone breakage (Aims 3 and 4), and 3) evaluate the efficacy and safety of newer generation lithotripters, including a promising dual pulse lithotripter (Aims 5 and 6). Project 2 experiments will be highly interactive with the other projects of this Program Project Grant. In collaboration with Projects 3 and 4 we will utilize high-speed photography, dual passive cavitation detection and B-scan ultrasound to determine the mechanism responsible for improved stone breakage at slow SW-rate, and will find the balance between SW-rate and power that gives improved stone comminution. In studies with Project 1 we will use a new animal model for stone implantation in the pig kidney and the ureter to help evaluate the effect of lithotfipter settings on stone breakage. With our colleagues in Projects 3 and 4 we will analyze cavitation bubble activity in vitro, to determine how the environment of a stone--that is, its tissue boundaries and the composition of the fluid that bathes the stoneminfluence cavitation bubble dynamics involved in stone fragmentation. Using our in vivo stone implantation model and our Project 1 animal model of renal injury in SWL, and in collaboration with projects 3 and 4, we will evaluate and compare the efficacy and safety of different types of lithotripters -- including the electrohydraulic Dornier HM3, the electromagnetic Dornier Compact Delta (a newer generation tight-focal-zone, high power machine), and the Direx Duet dual-pulse lithotripter. Thus, project 2 will find ways to improve how lithotripsy is performed using conventional lithotripters, evaluate newer machines so that we can learn to use them more safely and effectively, and test a promising new concept for dual pulse SW delivery that has the potential to improve SWL.